Mitochondrial impairment and synaptic dysfunction in AD. (A) Under pathological conditions, Aβ oligomers directly or indirectly affect mitochondrial fission proteins such as Drp1 and mitochondrial matrix proteins, including ABAD and CypD. Such interactions may mediate Aβ-induced mitochondrial fragmentation with consequent bioenergetics failure and resulting synaptic loss. (B) Synaptic mitochondria are more vulnerable to pathological toxins than non-synaptic mitochondria. Aβ is also more likely accumulated in synaptic mitochondria than in non-synaptic mitochondria, thus enhancing damage on synaptic mitochondria.